The enormous growth in the use of small animals for basic biomedical research has created a compelling need for new approaches to structural and functional phenotyping in the rodent. We propose continuation of the Duke Integrated Center for In Vivo Microscopy, an NIH/NCRR National Resource with an explicit focus on meeting this need. We propose four integrated cores that will provide researchers from around the world new image-based methods for structural and functional phenotyping using magnetic resonance microscopy (MRM). Core A: We will develop functional microscopy in the rodent to support cardiac motion analysis, pulmonary perfusion using arterial spin tagging and pulmonary ventilation using hypcrpolarized gas imaging. Core B: We will develop more efficient encoding strategies to increase our throughput for MR Histology by at least 500%. We will develop methods for actively staining fixed tissues for 3D MR histology. We will develop methods to measure regional neurodegeneration in the mouse brain. Core C: We will develop a new generation of technologies for physiologic support and monitoring of small animals permitting mutlimodality imaging (MRM. MicroPET, microCT, etc.) and image registration and long term studies on animals with compromised immunologic systems. Core D: We will develop visual informatics tools to permit effective archive, access, and analysis of very large multidimensional image sets from multiple modalities. The technologies will support a total of 16 collaborators anxious to use small animal imaging to extend the horizons of topics ranging from cancer to neurobiology. An aggressive education and dissemination program is included that will include undergraduate and graduate students, as well as post-doctoral fellows.